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Heart failure and cardiomyopathies
Cross sectional study or survey
Original research article
Pathophysiology of exercise intolerance in chronic diseases: the role of diminished cardiac performance in mitochondrial and heart failure patients
  1. Jodi McCoy1,
  2. Matthew Bates1,2,
  3. Christopher Eggett1,
  4. Mario Siervo1,
  5. Sophie Cassidy1,
  6. Jane Newman1,
  7. Sarah A Moore3,
  8. Grainne Gorman3,4,
  9. Michael I Trenell1,5,
  10. Lazar Velicki6,
  11. Petar M Seferovic7,
  12. John G F Cleland8,
  13. Guy A MacGowan9,
  14. Doug M Turnbull3,4 and
  15. Djordje G Jakovljevic1,10
  1. 1Institute of Cellular Medicine, Medical School, Newcastle University, Newcastle upon Tyne, UK
  2. 2Department of Cardiothoracic, The James Cook University Hospital, Middleborough, UK
  3. 3Institute of Neurosciences, Newcastle University, Newcastle upon Tyne, UK
  4. 4Wellcome Trust Centre for Mitochondrial Research, Newcastle University, Newcastle uponTyne, UK
  5. 5Research Councils UK Centre for Ageing and Vitality, Newcastle University, Newcastle upon Tyne, UK
  6. 6Department of Cardiovascular Surgery and Faculty of Medicine, Institute of Cardiovascular Diseases Sremska Kamenica, Novi Sad, Serbia
  7. 7Department of Cardiology, Clinical Centre Serbia, University of Belgrade, Serbia, UK
  8. 8Department of Cardiology, Imperial College Royal Brompton and Harefield Trust London, London, UK
  9. 9Department of Cardiology, Freeman Hospital and Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK
  10. 10Clinical Research Facility, Royal Victoria Infirmary, Newcastle upon Tyne, UK
  1. Correspondence to Dr Djordje G Jakovljevic, Institute of Cellular Medicine, The Medical School, Newcastle University, NE2 4HH. UK; d.jakovljevic{at}ncl.ac.uk

Abstract

Objective Exercise intolerance is a clinical hallmark of chronic conditions. The present study determined pathophysiological mechanisms of exercise intolerance in cardiovascular, neuromuscular, and metabolic disorders.

Methods In a prospective cross-sectional observational study 152 patients (heart failure reduced ejection fraction, n=32; stroke, n=34; mitochondrial disease, n=28; type two diabetes, n=28; and healthy controls, n=30) performed cardiopulmonary exercise testing with metabolic and haemodynamic measurements. Peak exercise O2 consumption and cardiac power output were measures of exercise tolerance and cardiac performance.

Results Exercise tolerance was significantly diminished in patients compared with controls (ie, by 45% stroke, 39% mitochondria disease, and 33% diabetes and heart failure, p<0.05). Cardiac performance was only significantly reduced in heart failure (due to reduced heart rate, stroke volume, and blood pressure) and mitochondrial patients (due reduced stroke volume) compared with controls (ie, by 53% and 26%, p<0.05). Ability of skeletal muscles to extract oxygen (ie, arterial-venous O2 difference) was diminished in mitochondrial, stroke, and diabetes patients (by 24%, 22%, and 18%, p<0.05), but increased by 21% in heart failure (p<0.05) compared with controls. Cardiac output explained 65% and 51% of the variance in peak O2 consumption (p<0.01) in heart failure and mitochondrial patients, whereas arterial-venous O2 difference explained 69% (p<0.01) of variance in peak O2 consumption in diabetes, and 65% and 48% in stroke and mitochondrial patients (p<0.01).

Conclusions Different mechanisms explain exercise intolerance in patients with heart failure, mitochondrial dysfunction, stroke and diabetes. Their better understanding may improve management of patients, their stress tolerance and quality of life.

  • exercise limitations
  • heart failure
  • cardiac function
  • oxygen consumption

This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/4.0/

https://doi.org/10.1136/openhrt-2017-000632

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    Footnotes

    • Contributors DGJ had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.Study concept and design:DGJ Acquisition of data: JMcC, MS, SC, JN, MB, GG, SAM. Statistical analysis and interpretation of data: JMcC, DGJ. Drafting of the manuscript: JMcC, DGJ. Critical revision of the manuscript for important intellectual content: MB, MG, CE, GG, MIT, JGFC, PMS, MIT, DGJ. Administrative, technical, or material support: JMcC, Cassidy, DGJ. Study Supervision: DGJ, MIT.

    • Funding This study was funded by the Newcastle National Institute for HealthResearch (NIHR) Biomedical Research Centre in Ageing and Age Related Diseases. DrSiervo is supported by the UK Medical Research Council investigator award, Gorman andNewman by the Welcome Trust Centre for Mitochondrial Diseases, Moore by the NIHRClinical Academic Lectureship, Trenell by NIHR Senior Research Fellowship, andJakovljevic by Research Councils UK Centre for Ageing and Vitality.

    • Competing interests None declared.

    • Ethics approval North East of England - Tyne and Wear South.

    • Provenance and peer review Not commissioned; internally peer reviewed.